title: Interactions of N'-acetyl-rifabutin and N'-butanoyl-rifabutin with lipid bilayers: a synchrotron X-ray study.
abstract: This work focuses on the interaction of N'-acetyl-rifabutin (RFB2) and N'-butanoyl-rifabutin (RFB3) with human and bacterial cell membrane models under physiological conditions. The effect of RFB2 and RFB3 on human cell membrane models was assessed using multilamellar vesicles (MLVs) composed of 1,2-dimyristoyl-rac-glycero-3-phosphocholine (DMPC). In order to mimic the bacterial cell membrane, MLVs of 1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DMPG) and a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) and 1,2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DPPG) (8:2 molar ratio) were chosen. Small and wide-angle X-ray scattering (SAXS and WAXS) were used to study the effect of these antimycobacterial compounds on the structure formed in aqueous lipid dispersions. This study contributes to understanding the molecular mechanisms of the drugs delivery through the human and bacterial cells and the effect of these antimycobacterial compounds on the membrane lipids organization, which is related with their antibiotic efficacy and toxic effects.
authors.affiliation: REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Portugal.
authors.forename: Marina
authors.initials: M
authors.lastname: Pinheiro
authors.forename: Cláudia
authors.initials: C
authors.lastname: Nunes
authors.forename: João M
authors.initials: JM
authors.lastname: Caio
authors.forename: Cristina
authors.initials: C
authors.lastname: Moiteiro
authors.forename: Gerald
authors.initials: G
authors.lastname: Brezesinski
authors.forename: Salette
authors.initials: S
authors.lastname: Reis
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001419:Bacteria; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry*; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000737:chemistry*; D017828:Rifabutin / Q000031:analogs & derivatives* / Q000737:chemistry*; D017356:Synchrotrons; D014965:X-Rays
chemical_list: D000900:Anti-Bacterial Agents; D008051:Lipid Bilayers; D010714:Phosphatidylethanolamines; D010715:Phosphatidylglycerols; D017828:Rifabutin; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; C002773:dimyristoylphosphatidylglycerol; D004134:Dimyristoylphosphatidylcholine
keywords: Cubic phases; Membrane models; Rifabutin; Small-angle X-ray scattering; Tuberculosis; Wide-angle X-ray scattering